Enteric pathogen exposure and child health in low-income settings Público
Goddard, Frederick (Spring 2020)
Published
Abstract
Background. Infections with enteric pathogens impair gastrointestinal function, causing diarrheal disease and nutritional deficits, the burden of which is highest among young children in low-income countries. Methods to estimate exposure to enteric pathogens suffer from a number of shortcomings, including the use of indicators of fecal contamination as proxies for enteric pathogens and that most exposure assessments estimate aggregate exposure (i.e. at the household- or community-level) instead of personal exposure. This dissertation sought to generate evidence to inform method development for improved measures of enteric exposure. Methods. The first aim estimated enteric exposure-health outcome relationships using household-level indicators of fecal contamination. We used an individual participant data (IPD) meta-analysis approach by requesting data from research identified through a systematic review. The second aim evaluated potential sources of measurement error in these proxy measures of exposure, by adapting an air pollution epidemiology exposure measurement error framework to drinking water quality. The third aim assessed the utility of saliva to estimate past exposure by measuring salivary antibody concentrations and comparing them to enteric pathogens detected in matched stool samples. Findings. Our IPD analyses found that fecal contamination in drinking water is associated with both diarrhea and impaired linear growth, and also implicated contaminated hands in diarrhea and contaminated fomites in stunted growth. The measurement error simulations suggested that household-level exposure assessments that do not consider exposure in the community may attenuate true water quality-diarrhea associations, particularly for older children. We also found that using single water quality measures, thereby not accounting for temporal variability in water quality, may attenuate the true effects of water quality on child growth. The saliva research found lower antibody concentrations in children experiencing higher numbers of concurrent enteric infections, and highlighted the need for further validation of salivary diagnostics for the detection of pathogen-specific antibodies. Conclusions. The findings from research conducted for this dissertation highlight the shortcomings of enteric exposure assessments. They also underline opportunities to improve methods used to estimate enteric exposure, which could subsequently contribute to informing policies and interventions designed to reduce the burden of enteric infections in underrepresented and underserved populations.
Table of Contents
1 Chapter 1: Introduction. 1
1.1 Motivation. 1
1.1.1 The need for improved exposure methods: the WaSH example. 5
1.2 Dissertation aims. 8
1.2.1 Research Aim 1. 9
1.2.2 Research Aim 2. 9
1.2.3 Research Aim 3. 9
1.3 References. 11
2 Chapter 2: Estimating enteric exposure: A review of approaches. 15
2.1 Context 15
2.2 External and internal exposure assessments. 15
2.3 Current approaches. 17
2.3.1 Criteria. 17
2.3.2 Measuring enteric pathogens in the environment 18
2.3.3 Measuring host interaction with the environment 26
2.3.4 Measuring enteric pathogens in humans. 29
2.4 Limitations of current approaches. 32
2.5 Lessons from other areas of environmental health. 34
2.5.1 Measurement error 34
2.5.2 Air quality. 34
2.5.3 Chemical Toxicants. 36
2.6 References. 37
2.7 1 References. 37
3 Chapter 3 – Research Aim 1: Fecal contamination of the environment and child health: A systematic review and meta-analysis using individual participant data. 45
3.1 Context 45
3.2 Background. 45
3.3 Methods. 47
3.3.1 Search strategy and selection criteria. 47
3.3.2 Data analysis. 48
3.4 Results. 51
3.5 Discussion. 59
3.6 References. 62
4 Chapter 4 – Research Aim 2: Exposure measurement error and the characterization of child exposure to fecal contamination in drinking water 65
4.1 Context 65
4.2 Background. 65
4.2.1 Exposure measurement error framework. 67
4.3 Methods. 70
4.3.1 Data. 70
4.3.2 Analytical approach. 70
4.3.3 Single versus Multiple Samples. 73
4.4 Results. 75
4.5 Discussion. 81
4.6 References. 86
5 Chapter 5 – Research Aim 3: Child salivary SIgA and its relationship to enteric infections and EED biomarkers in Maputo, Mozambique. 90
5.1 Context 90
5.2 Background. 90
5.3 Methods. 92
5.3.1 Study setting and participants. 92
5.3.2 Procedures. 93
5.3.3 Statistical analysis. 94
5.3.4 Ethics. 96
5.4 Results. 96
5.4.1 Summary characteristics. 96
5.4.2 Total SIgA and enteric infections. 97
5.4.3 Total SIgA and EED biomarkers. 99
5.4.4 Pathogen-specific SIgA.. 100
5.5 Discussion. 101
5.6 References. 105
6 Chapter 6: Summary, implications, future research and conclusion. 109
6.1 Summary of findings. 109
6.1.1 Limitations. 110
6.2 Implications. 111
6.3 Future research. 113
6.4 Conclusion. 116
6.5 References. 118
7 Appendices. 119
7.1 Appendix A – Research Aim 1: Search Strings. 120
7.2 Appendix B – Research Aim 1: Supplementary Figures. 121
7.3 Appendix C - Research Aim 1: Risk of Bias Assessments. 131
7.4 Appendix D – Research Aim 2: Sensitivity Analyses 133
About this Dissertation
| School | |
|---|---|
| Department | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| Palavra-chave | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
Enteric pathogen exposure and child health in low-income settings () | 2020-03-30 14:19:46 -0400 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|